Your Digest for Thursday, Sep 07, 2023 06:59 PM


#2021BSQ-NOV Q31
These are more clearly seen in type I DM.
In type 2 DM, vascular and tubulointerstitial changes predominate.

  1. changes in glomerular hemodynamics
    1. DM -> somehow ↑ RAAS activity -> increased GFR -> In early stages of DM: Glomerular hyperfiltration.
    2. Glomerular HYPERFILTRATION is a recognized phenomenon in early diabetes.
    3. Hyperfiltration is associated with increased risk of progression of kidney function decline.
    4. Also, renal autoregulation of blood flow may be impaired - exposing the kidney to effects of hypertension. => increased GFR
  2. Oxidative stress and inlammation
    1. DM -> Advanced Glycation End products (AGE) -> inflammation
  3. Interstitial fibrosis and tubular atrophy.
    1. DM -> Hyperglycaemia -> ↑ activity of hexosamine pathway +↑ RAAS acvitity -> ↑ TGF-Beta production -> fibrosis and atrophy
Glomerular changes

Mesangial proliferation -> further proliferation + matrix deposition -> PAS positive kimmelstiel-Wilson bodies.

  1. Diffuse basement membrane thickening along it's entire length
  2. Diffuse mesangial sclerosis <- diffuse increase of mesangial cells and matrix.
  3. Nodular glomerular sclerosis <- a pattern of sclerosis with nodules of matrix at the periphery of the glomerulus. AKA Kimmelstiel Wilson nodules. <- Pathognomonic of DM (almost)
    These changes are present in all patients with renal impairment in T1 DM.
Chronological sequence of changes
  1. Glomerular basement membrane thickening is the first to be seen.
  2. Thickening of the tubular basement membrane parallels GBM thickening.
  3. Mesangial proliferation and sclerosis is seen later.

[!INFO]
This 'neat' sequence is best observed in type 1 DM. It's more complicated in Type 2

Non glomerular changes

[!INFO]
diabeticNephropathyHistologySclerosis.jpg
Glomerulus from a type 1 diabetic (T1DM) patient with diffuse (long thick arrow) and nodular (short thick arrow) mesangial expansion and afferent (double thin arrows) and efferent (single thin arrow) arteriolar hyalinosis. Source

DMKimmelstielWilsonBodies.png


[!INFO] Is an autoimmume, T cell infiltrative disease.
#2021BSQ-NOV Q32


#2021BSQ-NOV Q31

Leukemoid reaction refers to a white blood cell (WBC) count >50,000/microL from causes other than leukemia. (Usually severe reaction to an infection).

The majority of cells are mature neutrophils, but often accompanied by a prominent left shift.

[!INFO] Left shift
"Left shift" : ill defined term meaning increased band forms, myelocytes and metamyelocytes. -> indicates infection, sepsis of chronic myeloid leukemia.
Myelocytes are neutrophil precursors seen mainly in bone marrow. Metamyelocytes are their descendants, and can be seen in the blood.
Greek "meta" means 'after'.
Band forms are immature neutrophils whose nucleus hasn't yet become segmented and have a C or S shape.

Some Causes:

Clues for cause or neutrophilia:

  1. Toxic granules present or Dohle bodies -> Infection / inflammation
  2. Left shift -> infection or Chronic myeloid leukemia.
  3. Significant number of myeloid blasts -> Acute myeloid leukemia

Spurious neutrophilia / false neurophilia / pseudo neutrophilia:
interferrenace with the particle counter can case false neutrophelia in


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Cellular adaptations

#2021BSQ-NOV Q34

Hyperplasia and hypertrophy

Important points:

Atrophy

Causes:

[!INFO] Definition of atrophy
In atrophy, a shell shrinks to a smaller size with reduced function so that it can survive under the new (less conducive) growth conditions imposed by factors listed above.
Atrophic cells are not dead.
Cellular mechanisms:

Metaplasia

metaplasiaMnemonic.png
Reprogramming of stem cells to differentiate into a cell type that is more suitable to cope with the new stresses than the original cell type at that location.
I.e results in replacement of one type of mature cell with another type of mature cell.
It is a reversible change;
Example: Squamous metaplasia of respiratory epithelium in smokers.
Vitamin A is essential for normal epithelial differentiation.

Pathology of cancers

Anaplasia

Anaplasia: "backward formation" - loss of structural and functional differentiation of cells. A hallmark of malignancy

[!INFO] Dedifferentiation Vs. Lack of differentiation
There may be some technical difference between dedifferentiation and inability to differentiate at all (as seen in cancers of stem cells)
See Robbins (Page 165).

Pathologic features of anaplastic cells:

AnaplasticCellsFeatures.png

Dysplasia

Dysplasia:

Infectious causes of cancer

==From Wikipedia==

Agent Malignancy
Viruses
HPV Cervical carcinoma, Nasopharyngeal carcinoma (less association than EBV)
EBV Lymphomas, nasopharyngeal carcinoma
Kaposi Sarcoma herpevirus Kaposi sarcoma
Hepatitis B and C HCC
Human T cell leukemia virus Adult T cell leukemia
-
Bacteria
H pylori Gastric cancer
-
Parasites
Schistosoma SQC of bladder
Chlornorchis sinensis Cholangiocardinoma


Gatric cancer can be

H. pylori and gastric cancer

H pylori infection is associated with several types of gastric cancer.
Treatment of H pylori infection reduces cancer risk.
The exact mechanism is not known but there are several theories.

Types of cancer associated with H. pylori:

(AKA TNF-alpha, AKA TNF-α, aka cachexin)

  1. mitochondrial or intrinsic pathway => promoted by DNA damange and accumulation of misfolded proteins. Pro apoptotic proteins leak out of the mitrochondria; This pathway is inhibited when the cell receives growth signals.

Endothelial cell contraction occurs rapidly after binding of histamine, bradykinin, leukotrienes, and many other mediators to specific receptors, and is usually short-lived (15 to 30 minutes). A slower and more prolonged retraction of endothelial cells, resulting from changes in the cytoskeleton, may be induced by cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1).

  1. TNF
    TNF and IL-1 : the main role of TNF and IL-1 is in endothelial cell activation which causes increased vascular permeability and increased expression of adhesion molecules to facilitate phagocyte (neutrohil) migration and to enhance production of chemokines and other cytokines.

Hürthle cell carcinoma is a rare, more agrressive variant of follicular carcinoma. 5 year survival is 50 - 60%.

[!INFO] Hurthle cells are seen in non malignant conditions as well
Hurthle cells are clasically seen in


#2021BSQ-NOV Q33

+ve APR -ve APR
Fibrinogen(large effect on ESR) Albumin
Haptoglobin Transferrin
Alpha 1 antitrypsin - protease inhibitor Antithrombin
Hepcidin - hormone controlling iron absorption retinol binding protein
procalcitonin
[[Anaemia#Iron metabolism and iron studies|Ferritin]]
Serum amyloid A: Rises x1000 during acute phase. Role unkown. Maybe cytokines Source

"For F*cks Sake, Protect Harry's Ass Hole " - +ve acute phase reactancts.
happyPotterAcutePhaseMnemonic.png